DOI QR코드

DOI QR Code

Protective role of paeoniflorin from hydrogen peroxide-mediated oxidative damage in C6 glial cells

  • Lee, Ah Young (Department of Food Science, Gyeongnam National University of Science and Technology) ;
  • Nam, Mi Na (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Kim, Hyun Young (Department of Food Science, Gyeongnam National University of Science and Technology) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University)
  • Received : 2020.02.11
  • Accepted : 2020.03.24
  • Published : 2020.06.30

Abstract

Oxidative stress is one of the pathogenic mechanisms of various neurodegenerative diseases, such as Alzheimer's disease. Neuroglia, the most abundant cells in the brain, is thought to play an important role in the antioxidant defense system and neuronal metabolic support against neurotoxicity and oxidative stress. We investigated the protective effect of paeoniflorin (PF) against oxidative stress in C6 glial cells. Exposure of C6 glial cells to hydrogen peroxide (H2O2, 500 μM) significantly decreased cell viability and increased amounts of lactate dehydrogenase (LDH) release, indicating H2O2-induced cellular damage. However, treatment with PF significantly attenuated H2O2-induced cell death as shown by increased cell survival and decreased LDH release. The H2O2-stimulated reactive oxygen species production was also suppressed, and it may be associated with improvement of superoxide dismutase activity by treatment with PF. In addition, an increase in ratio of Bcl-2/Bax protein expression was observed after treatment with PF. In particular, the down-stream of the apoptotic signaling pathway was inhibited in the presence of PF, mostly by reduction of cleaved-poly ADP ribose polymerase, cleaved caspase-3, and -9 protein expression. Furthermore, H2O2-induced phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 was attenuated by treatment with PF. Taken together, neuroprotective effect of PF against oxidative stress probably result from the regulation of apoptotic pathway in C6 glial cells. In conclusion, our findings suggest that PF may be a potent therapeutic agent for neurodegenerative disorders.

Keywords

References

  1. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59: 1609-1623 https://doi.org/10.1111/j.1471-4159.1992.tb10990.x
  2. Bains JS, Shaw CA (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Rev 25: 335-358 https://doi.org/10.1016/S0165-0173(97)00045-3
  3. Sies H (2017) Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress. Redox Biol 11: 613-619 https://doi.org/10.1016/j.redox.2016.12.035
  4. Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2: 679-689 https://doi.org/10.1038/ncpneuro0355
  5. Shimohama S (2000) Apoptosis in Alzheimer's disease-an update. Apoptosis 5: 9-16 https://doi.org/10.1023/A:1009625323388
  6. Takata K, Kitamura Y, Yanagisawa D, Morikawa S, Morita M, Inubushi T, Tsuchiya D, Chishiro S, Saeki M, Taniguchi T, Shimohama S, Tooyama I (2007) Microglial transplantation increases amyloid-beta clearance in Alzheimer model rats. FEBS Lett 581: 475-478 https://doi.org/10.1016/j.febslet.2007.01.009
  7. Lopategui Cabezas I, Herrera Batista A, Penton Rol G (2014) The role of glial cells in Alzheimer's disease: potential therapeutic implications. Neurologlia 29: 305-309 https://doi.org/10.1016/j.nrl.2012.10.006
  8. Xiao L, Wang YZ, Liu J, Luo XT, Ye Y, Zhu XZ (2005) Effects of paeoniflorin on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of transient middle cerebral artery occlusion in rats. Life Sci 78: 413-420 https://doi.org/10.1016/j.lfs.2005.04.069
  9. Ohta H, Matsumoto K, Shimizu M, Watanabe H (1994) Paeoniflorin attenuates learning impairment of aged rats in operant brightness discrimination task. Pharmacol Biochem Behav 49: 213-217 https://doi.org/10.1016/0091-3057(94)90478-2
  10. Mao QQ, Zhong XM, Li ZY, Huang Z (2011) Paeoniflorin protects against NMDA-induced neurotoxicity in PC12 cells via $Ca^{2+}$ antagonism. Phytother Res 25: 681-685 https://doi.org/10.1002/ptr.3321
  11. Lee G, Joo JC, Choi BY, Lindroth AM, Park SJ, Park YJ (2016) Neuroprotective effects of Paeonia lactiflora extract against cell death of dopaminergic SH-SY5Y cells is mediated by epigenetic modulation. BMC Complement Altern Med 16: 208 https://doi.org/10.1186/s12906-016-1205-y
  12. Kim SH, Lee MK, Lee KY, Sung SH, Kim J, Kim YC (2009) Chemical constituents isolated from Paeonia lactiflora roots and their neuroprotective activity against oxidative stress in vitro. J Enzyme Inhib Med Chem 24: 1138-1140 https://doi.org/10.1080/14756360802667977
  13. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63 https://doi.org/10.1016/0022-1759(83)90303-4
  14. Racher AJ, Looby D, Griffiths JB (1990) Use of lactate dehydrogenase release to assess changes in culture viability. Cytotechnology 3: 301-307 https://doi.org/10.1007/BF00365494
  15. Cathcart R, Schwiers E, Ames BN (1983) Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay. Anal Biochem 134: 111-116 https://doi.org/10.1016/0003-2697(83)90270-1
  16. Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39: 73-82 https://doi.org/10.1080/01616412.2016.1251711
  17. Rodriguez JJ, Olabarria M, Chvatal A, Verkhratsky A (2009) Astroglia in dementia and Alzheimer's disease. Cell Death Differ 16: 378-385 https://doi.org/10.1038/cdd.2008.172
  18. Bronstein DM, Perez-Otano I, Sun V, Mullis Sawin SB, Chan J, Wu GC, Hudson PM, Kong LY, Hong JS, McMillian MK (1995) Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures. Brain Res 704: 112-116 https://doi.org/10.1016/0006-8993(95)01189-7
  19. Ramalingam M, Kim SJ (2016) Insulin involved Akt/ERK and Bcl-2/Bax pathways against oxidative damages in C6 glial cells. J Recept Signal Transduct Res 36: 14-20 https://doi.org/10.3109/10799893.2014.970276
  20. Rossi DJ, Brady JD, Mohr C (2007) Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10: 1377-1386 https://doi.org/10.1038/nn2004
  21. Shibata N, Kobayashi M (2008) The role for oxidative stress in neurodegenerative diseases. Brain Nerve 60: 157-170
  22. Makar TK, Nedergaard M, Preuss A, Gelbard AS, Perumal AS, Cooper AJL (1994) Vitamin E, ascorbate, glutathione disulfide, and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: evidence that astrocytes play an important role in antioxidative processes in the brain. J Neurochem 62: 45-53 https://doi.org/10.1046/j.1471-4159.1994.62010045.x
  23. Delacourte A (1990) General and dramatic glial reaction in Alzheimer brain. Neurology 40: 33-37 https://doi.org/10.1212/WNL.40.1.33
  24. Winterbourn CC (2013) The biological chemistry of hydrogen peroxide. Methods Enzymol 528: 3-25 https://doi.org/10.1016/B978-0-12-405881-1.00001-X
  25. Hamdi Y, Masmoudi-Kouki O, Kaddour H, Belhadj F, Gandolfo P, Vaudry D, Mokni M, Leprince J, Hachem R, Vaudry H, Tonon MC, Amri M (2011) Protective effect of the octadecaneuropeptide on hydrogen peroxide-induced oxidative stress and cell death in cultured rat astrocytes. J Neurochem 118: 416-428 https://doi.org/10.1111/j.1471-4159.2011.07315.x
  26. Wu YM, Jin R, Yang L, Zhang J, Yang Q, Guo YY, Li XB, Liu SB, Luo XX, Zhao MG (2013) Phospyatidylinositol 3 kinase/protein kinase B is responsible for the protection of paeoniflorin upon $H_2O_2$-induced neural progenitor cell injury. Neuroscience 240: 54-92 https://doi.org/10.1016/j.neuroscience.2013.02.037
  27. Li P, Li Z (2015) Neuroprotective effect of paeoniflorin on $H_2O_2$-induced apoptosis in PC12 cells by modulation of reactive oxygen species and the inflammatory response. Exp Ther Med 9: 1768-1772 https://doi.org/10.3892/etm.2015.2360
  28. Lee SM, Yoon MY, Park HR (2008) Protective effects of Paeonia lactiflora Pall on hydrogen peroxide-induced apoptosis in PC12 cells. Biosci Biotechnol Biochem 72: 1272-1277 https://doi.org/10.1271/bbb.70756
  29. Whittemore ER, Loo DT, Cotman CW (1994) Exposure to hydrogen peroxide induces cell death via apoptosis in cultured rat cortical neurons. Neuroreport 5: 1485-1488 https://doi.org/10.1097/00001756-199407000-00019
  30. Jang JH, Surh YJ (2001) Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. Mutat Res 496: 181-190 https://doi.org/10.1016/S1383-5718(01)00233-9
  31. Roychowdhury S, Wolf G, Keihoff G, Bagchi D, Horn T (2001) Protection of primary glial cells by grape seed proanthocyanidin extract against nitrosative/oxidative stress. Nitric Oxide 5: 137-149 https://doi.org/10.1006/niox.2001.0335
  32. Li CR, Zhou Z, Zhu D, Sun YN, Dai JM, Wang SQ (2007) Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. Int J Biochem Cell Biol 39: 426-438 https://doi.org/10.1016/j.biocel.2006.09.011
  33. Kwon SH, Hong SI, Ma SX, Lee SY, Jang CG (2015) 3',4',7-trihydroxyflavone prevents apoptotic cell death in neuronal cells from hydrogen peroxide-induced oxidative stress. Food Chem Toxicol 80: 41-51 https://doi.org/10.1016/j.fct.2015.02.014
  34. Bray RC, Cockle SA, Fielden EM, Roberts PB, Rotilio G, Calabrese L (1974) Reduction and inactivation of superoxide dismutase by hydrogen peroxide. Biochem J 139: 43-48 https://doi.org/10.1042/bj1390043
  35. Li W, Qi Z, Wei Z, Liu S, Wang P, Chen Y, Zhao Y (2015) Paeoniflorin inhibits proliferation and induces apoptosis of human glioma cells via microRNA-16 upregulation and matrix metalloproteinase-9 downregulation. Mol Med Rep 12: 2735-2740 https://doi.org/10.3892/mmr.2015.3718
  36. Mahesh R, Kim SJ (2009) The protective effect of insulin on hydrogen peroxide-induced oxidative stress in C6 glial cells. Biomol Ther 17: 395-402 https://doi.org/10.4062/biomolther.2009.17.4.395
  37. Richter-Landsberg C, Vollgraf U (1998) Mode of cell injury and death after hydrogen peroxide exposure in cultured oligodendroglia cells. Exp Cell Res 244: 218-229 https://doi.org/10.1006/excr.1998.4188
  38. Susnow N, Zeng L, Margineantu D, Hockenbery DM (2009) Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol 19: 42-49 https://doi.org/10.1016/j.semcancer.2008.12.002
  39. Kane DJ, Sarafian TA, Anton R, Hahn H, Gralla EB, Valentine JS, Ord T, Bredesen DE (1993) Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262: 1274-1277 https://doi.org/10.1126/science.8235659
  40. Kirkland RA, Saavedra GM, Cummings BS, Franklin JL (2010) Bax regulates production of superoxide in both apoptotic and nonapoptotic neurons: role of caspases. J Neurosci 30: 16114-16127 https://doi.org/10.1523/JNEUROSCI.2862-10.2010
  41. Jiang X, Wang X (2004) Cytochrome C-mediated apoptosis. Annu Rev Biochem 73: 87-106 https://doi.org/10.1146/annurev.biochem.73.011303.073706
  42. Chaitanya GV, Alexander JS, Babu PP (2010) PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal 8: 31 https://doi.org/10.1186/1478-811X-8-31
  43. Sun R, Wan K, Wu D, Li X, Ou Y (2012) Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway. Folia Neuropathol 50: 270-276
  44. Wu YM, Xu HP, Wang CT, Yang H, Ju G (2002) Protective effects of paeoniflorin on cultured cortical neurons of mice. Chin. J Pharmacol Toxicol 16: 172-175
  45. Dutta K, Ghosh D, Basu A (2009) Curcumin protects neuronal cells from Japanese encephalitis virus-medicated cell death and also inhibits infective viral particle formation by dysregulation of ubiquitinproteasome system. J Neuroimmune Pharmacol 4: 328-337 https://doi.org/10.1007/s11481-009-9158-2
  46. Patraca I, Martinez N, Busquets O, Marti A, Pedros I, Beas-Zarate C, Marin M, Ettcheto M, Sureda F, Auladell C, Camins A, Folch J (2017) Anti-inflammatory role of leptin in glial cells through p38 MAPK pathway inhibition. Pharmacol Rep 69: 409-418 https://doi.org/10.1016/j.pharep.2016.12.005
  47. Kwon DY, Kim SJ, Lee JW, Kim YC (2010) Comparison of hydroxyl radial, peroxyl radical, and peroxynitrite scavenging capacity of extracts and active components from selected medicinal plants. Toxicol Res 26: 321-327 https://doi.org/10.5487/TR.2010.26.4.321
  48. Lin X, Wu S, Wang Q, Shi Y, Liu G, Zhi J, Wang F (2016) Saikosaponin-D reduces $H_2O_2$-indcued PC12 cell apoptosis by removing ROS and blocking MAPK-dependent oxidative damage. Cell Mol Neurobiol 36: 1365-1375 https://doi.org/10.1007/s10571-016-0336-5
  49. Gu X, Cai Z, Cai M, Liu K, Zhang Q, Tan J, Ma Q (2016) Protective effect of paeoniflorin on inflammation and apoptosis in the cerebral cortex of a transgenic mouse model of Alzheimer's disease. Mol Med Rep 13: 2247-2252 https://doi.org/10.3892/mmr.2016.4805
  50. Wankun X, Wenzhen Y, Min Z, Weiyan Z, Huan C, Wei E, Lvzhen H, Xu Y, Xiaoxin L (2011) Protective effect of paeoniflorin against oxidative stress in human retinal pigment epithelium in vitro. Mol Vis 17: 3512-3522
  51. Ohta H, Ni JW, Matsumoto K, Watanabe H, Shimizu M (1993) Paeony and its major constituent, paeoniflorin, improve radial maze performance impaired by scopolamine in rats. Pharmacol Biochem Behav 45: 719-723 https://doi.org/10.1016/0091-3057(93)90530-7
  52. Sun L, Chen Y, Hou C, Sun X, Wang Z, Li S, Lv M, Chen X (2018) Neuroprotective effect of total glycosides from paeonies against neurotoxicity induced by strychnos alkaloids related to recovering the levels of neurotransmitters and neurodendocrine hormones in rat serum and brain. RSC Adv 8: 29210-29219 https://doi.org/10.1039/c8ra05384g
  53. Cao C, He X, Wang W, Zhang L, Lin H, Du L (2006) Kinetic distribution of paeoniflorin in cortex of normal and cerebral ischemiareperfusion rats after intravenous administration of Paeoniae Radix extract. Biomed Chromatogr 20: 1283-1288 https://doi.org/10.1002/bmc.658
  54. Tanaka T, Kataoka M, Tsuboi N, Kouno I (2000) New monoterpene glycoside esters and phenolic constituents of Paeoniae radix, and increase of water solubility of proanthocyanidins in the presence of paeoniflorin. Chem Pharm Bull 48: 201-207 https://doi.org/10.1248/cpb.48.201
  55. He X, Xing D, Ding Y, Li Y, Xiang L, Wang W, Du, L (2004) Determination of paeoniflorin in rat hippocampus by high-performance liquid chromatography after intravenous administration of Paeoniae Radix extract. J Chromatogr B Analyt Technol Biomed Life Sci 802: 277-281 https://doi.org/10.1016/j.jchromb.2003.11.040